期刊
JOURNAL OF INVESTIGATIVE DERMATOLOGY
卷 126, 期 4, 页码 855-861出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.jid.5700180
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- NIAMS NIH HHS [5 R01 AR45427-04] Funding Source: Medline
Photoprotection of the skin is provided by melanocytes, neural crest derived cells that synthesize melanin in specialized organelles that are transferred to keratinocytes. Secretory phospholipases comprise a large family of Ca2+-dependent enzymes that liberate arachidonic acid (AA), a precursor of prostaglandins, as well as lysophospholipids. The predominant secretory phospholipase expressed by keratinocytes is group X secretory phospholipase A(2) (sPLA(2)), which liberates large amounts of AA and the lysophospholipid lysophosphatidylcholine (LPC), from membrane preparations. Recent work by our laboratory has shown that melanocytes express receptors for prostaglandins that upon activation stimulate melanocyte dendricity and activity of tyrosinase, a key enzyme in melanin biosynthesis. In the present study, we have treated human melanocytes with recombinant sPLA(2)-X and show that low levels of sPLA(2)-X stimulate both tyrosinase activity and melanocyte dendricity. We found that the effects of sPLA(2)-X are mediated predominantly by LPC, not AA, and we have demonstrated expression of the phospholipase A(2) receptor and two G-protein-coupled receptors for LPC (G2A and GPR119) in human melanocytes. Because secretory phospholipases are released during inflammation and are regulated by UV irradiation, our data suggest an important role for sPLA(2)-X in cutaneous pigmentation through the release of LPC.
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